title: Conjugation of glucosamine with Gd3+-based nanoporous silica using a heterobifunctional ANB-NOS crosslinker for imaging of cancer cells.
abstract: BACKGROUND
  The aim of this study was to synthesize Gd(3+)-based silica nanoparticles that conjugate easily with glucosamine and to investigate their use as a nanoprobe for detection of human fibrosarcoma cells.
  
  
  METHODS
  Based on the structure of the 2-fluoro-2-deoxy-D-glucose molecule ((18)FDG), a new compound consisting of D-glucose (1.1 nm) was conjugated with a Gd(3+)-based mesoporous silica nanoparticle using an N-5-azido-2-nitrobenzoyloxy succinimide (ANB-NOS) crosslinker The contrast agent obtained was characterized using a variety of methods, including Fourier transform infrared spectroscopy, nitrogen physisorption, thermogravimetric analysis, scanning and transmission electron microscopy, and inductively coupled plasma atomic emission spectrometry (ICP-AES). In vitro studies included cell toxicity, apoptosis, tumor necrosis factor-alpha, and hexokinase assays, and in vivo tests consisted of evaluation of blood glucose levels using the contrast compound and tumor imaging. The cellular uptake study was validated using ICP-AES. Magnetic resonance relaxivity of the contrast agent was determined using a 1.5 Tesla scanner.
  
  
  RESULTS
  ANB-NOS was found to be the preferred linker for attaching glucosamine onto the surface of the mesoporous silica nanospheres. The r1 relaxivity for the nanoparticles was 17.70 mM(-1)s(-1) per Gd(3+) ion, which is 4.4 times larger than that for Magnevist® (r1 approximately 4 mM(-1)s(-1) per Gd(3+) ion). The compound showed suitable cellular uptake (75.6% ± 2.01%) without any appreciable cytotoxicity.
  
  
  CONCLUSIONS
  Our results suggest that covalently attaching glucosamine molecules to mesoporous silica nanoparticles enables effective targeted delivery of a contrast agent.
authors.affiliation: Biomedical Engineering and Medical Physics Department, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Bita
authors.initials: B
authors.lastname: Mehravi
authors.forename: Mohsen
authors.initials: M
authors.lastname: Ahmadi
authors.forename: Massoud
authors.initials: M
authors.lastname: Amanlou
authors.forename: Ahmad
authors.initials: A
authors.lastname: Mostaar
authors.forename: Mehdi Shafiee
authors.initials: MS
authors.lastname: Ardestani
authors.forename: Negar
authors.initials: N
authors.lastname: Ghalandarlaki
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000138:chemical synthesis / Q000493:pharmacokinetics; D003432:Cross-Linking Reagents / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D005944:Glucosamine / Q000737:chemistry / Q000493:pharmacokinetics*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging / Q000379:methods; D053769:Nanocapsules / Q000737:chemistry / Q000648:ultrastructure; D058608:Nanopores / Q000648:ultrastructure*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D003432:Cross-Linking Reagents; D053769:Nanocapsules; D012822:Silicon Dioxide; D005682:Gadolinium; D005944:Glucosamine
keywords: N-5-azido-2-nitrobenzoyloxy succinimide; gadolinium; glucosamine; magnetic resonance imaging; mesoporous silica nanospheres; photoactivation